genetic divergence

The rate of neutral mutations varies across the genome. When studying a single gene, this variation in rates is not especially important -- it is generally possible to obtain an estimate of the neutral rate for a single locus by comparing just that locus among closely related species.

But some comparisons involve looking at the pattern of variation among different loci. For instance, testing hypotheses about the ancestral populations leading to living species (like the common ancestor of humans and chimpanzees) involves comparing the amount of divergence among many independent loci. The variance in divergence times among loci gives an estimate of inbreeding in the ancestral population.

I discussed this particular example two years ago this week, after the paper that proposed extended hybridization between ancestral hominids and chimpanzees. The conclusion of the paper was that the X chromosome displays much less divergence between humans and chimpanzees than the autosomes, and this might reflect a late introgression of the X chromosome into hominids from another population that (mostly) was ancestral to chimpanzees. The autosomes, by contrast, averaged very old genetic divergences, although there was substantial variance. As I concluded then, the data look consistent with a large population size in the human-chimpanzee ancestor species, coupled with greater selection on the X chromosome. The interpretation of large population size (or alternatively, the interpretation of long-term population structure) comes from the low inferred inbreeding in that ancestral population -- which caused the variance in divergence dates among loci.

But there is another reason for a large variance in divergence dates: variance in mutation rates. Whenever mutation rates vary among loci, this variance adds to the variance among loci in their between-species genetic differences -- that is, the substitution rate. And as long as we are excluding selected sites (as we always try to do for these kinds of comparisons) we will overestimate the genetic diversity in ancestral species whenever the mutation rate varies among loci.

A new paper by Svitlana Tyakucheva and colleagues looks at human and macaque genomes to find patterns underlying the variance in mutation rates among regions of the genome. They find that a number of factors may cause such variations, including chemical factors like the CG content of the genome, functional causes such as male versus female rates of recombination, and large-scale structural causes such as telomeric proximity:

While a complete understanding of all biological mechanisms leading to variation in neutral substitution rates across the genome remains elusive, it is plausible that at least some of these mechanisms are conserved over relatively long evolutionary distances. For instance, both mouse-specific and rat-specific substitution rates are positively correlated with rodent-primate substitution rates [14], suggesting shared mechanisms persisting over ca. 90 million years [15]. Additionally, a positive correlation exists in substitution rates of homologous X- and Y-chromosomal introns that diverged from each other ca. 100 million years ago [16] (Tykucheva et al. 2008: R76).

Their finding that male recombination is an important contributor to mutation rate heterogeneity puts the focus on the X chromosome -- which has little recombination in males -- as unusual. X versus autosomal position did not explain a large fraction of the variance in this study (only around 2 percent, controlling for other factors) but the deviation was in the right direction to help account for the low X chromosome divergence between humans and chimpanzees.

Altogether in this study, a large fraction of variation in the human-macaque substitution variability could be explained by phenomena that affect the rate of mutations, including the structural and functional factors listed above as well as the corresponding homologous variability between mice and rats, and dogs and cattle. If these variations were explained by inbreeding in the human-macaque ancestral species, they would be random with respect to the dog-cow or mouse-rat divergences, and with respect to structural causes. So current estimates of the effective sizes of human-chimpanzee and other ancestral populations are almost certainly inflated. The amount of inflation is not clear, but a good estimate will require correcting for a large number of factors -- a complicated analysis.

Since the date of the human-chimpanzee divergence depends on our assessment of the diversity within the human-chimpanzee ancestral population, it may be a while before we can settle the issue of human-chimpanzee divergence time. That may or may not provide hope for Sahelanthropus, Orrorin, and Ardipithecus kadabba -- all supposed hominids that would predate 5 million years ago, the current best genetic estimate of the human-chimpanzee divergence time. To be sure, if the date is simply in error, that error might encompass older dates consistent with a 7-million-year divergence. But I'm not sure we should believe that the error is biased toward an older divergence -- "error" might lean in either direction, and a younger species divergence remains possible.

References:

Tyakucheva S, Makova KD, Karro JE, Hardison RC, Miller W, Chiaromonte F. 2008. Human-macaque comparisons illuminate variation in neutral substitution rates. Genome Biol 9:R76. doi:10.1186/gb-2008-9-4-r76

Out of this week's Science Times special on evolution, I clicked into John Noble Wilford's article first, titled "The Human Family Tree Has Become a Bush With Many Branches".

Now, I don't know about you, but that seems like a boring headline to me. They've been talking about human evolution being a bush for going on 20 years now. It was an old idea when I was in graduate school. So it seems like, if this is all we have going on, the "new frontier" of paleoanthropology must be pretty dull.

The writer doesn't write the headlines, and the headline doesn't describe Wilford's story, which is basically a verbal slide show of fossil discoveries over the last decade or so. Some bone pictures (of the actual species discussed) accompany the article, and it's a good enough sort of account of new finds since 1990, framed around the tension between fossil finders and molecule mavens.

But I'll be a little critical. The thesis is that paleoanthropologists suffered a crisis of confidence after molecular data came online in the 1980's, and "a rapid succession of fossil discoveries since the early 1990's has restored" it.

Well, OK, maybe. But consider the listed discoveries: Kenyanthropus, Ardipithecus ramidus, Ardipithecus ramidus, Orrorin tugenensis, Sahelanthropus tchadensis, Homo floresiensis, and Australopithecus anamensis. Of all of these, only Ar. ramidus and Au. anamensis have gone without significant controversy.

We can set aside H. floresiensis for a moment -- the controversy about it being possibly the loudest, it also stands apart as the only species listed younger than 3.9 million years. All of these early Pliocene and Miocene species have also been challenged -- by the discoverers of the others, by old hands, and by young upstarts like me. At least one research group has claimed that all of the Miocene "genera" may actually belong to one species. Another has claimed that most of these "hominids" may actually be apes.

Whether there was any crisis of confidence among paleoanthropologists, all this disagreement is certainly business as usual.

And, contrary to the article, every one of these species would be thrown from the hominid line, if we believe the molecules. Here's the text from the article:

Genetic clues also set the approximate time of the divergence of the human lineage from a common ancestor with apes: between six million and eight million years ago.

Fossil researchers were skeptical at first, a reaction colored perhaps by their dismay at finding scientific poachers on their turf. These paleoanthropologists contended that the biologists' "molecular clocks" were unreliable, and in some cases they were, though apparently not to a significant degree.

...

The new finds have filled in some of the yawning gaps in the fossil record. They have doubled the record's time span from 3.5 million back almost to 7 million years ago and more than doubled the number of earliest known hominid species. The teeth and bone fragments suggest the form -- the morphology -- of these ancestors that lived presumably just this side of the human-ape split.

It is true that the new fossils date as far back as 7 million years; with Sahelanthropus just under that date, Orrorin at around 6 million, Ar. kadabba at 5.5, Ar. ramidus at 4.4, and Au. anamensis at around 4.1.

But it has been many years since a genetic comparison indicated a human-chimpanzee common ancestor as old as 6-8 million years. This year's study by Holbolth et al. (2007) estimated a human-chimpanzee speciation time of 4.1 +/- 0.4 million years. That makes Au. anamensis possibly too young to be a hominid. The rest of those species would presumably be just so many apes.

Now, I don't believe for a second that Au. anamensis is an ape and not a hominid. It just looks too much like Au. afarensis -- so much so that some would put them in the same species. The evolutionary transition between these two is well documented, and will be more so when some as-yet-unpublished fossils come out. So anything younger than 4.1 million years is almost certainly not right for the human-chimpanzee divergence.

But the 4.1 million year estimate is not unusual compared to other recent studies. My post from last May covers many of these recent studies, including last year's problematic "hominid-chimpanzee hybrid speciation" paper by Nick Patterson and colleagues. The conclusion in that paper about hybridization was certainly wrong, but the date of 5 million years was right in line with other estimates.

These genetic comparisons are not easily dismissed. Possibly there has been a rate deceleration of mutations in the human lineage that means that the estimated dates are too recent. Maybe 4.1 million years can be stretched into 6 million. Maybe it can even be stretched into 7 million. But all this stretching does have other effects -- on the estimated dates of earlier divergences -- and those are compounded by a large multiple of the few million years we may try to push the human-chimpanzee speciation date. That 4.1 million year estimate is calibrated from an African-Asian great ape divergence at 18 million years ago. Push the human-chimpanzee divergence to 7 million, and you push the orangutan-human divergence back into the Oligocene. Are silent sites in humans evolving more slowly than cercopithecines? Probably. Are they evolving that much slower than orangutans? I suppose nothing is impossible, but maybe we should take another look at those fossils.

All this is to point out that there really is a conflict between these Miocene "hominids" and genomic evidence about human-chimpanzee speciation time. I don't see any magic solution to this problem from the molecular side -- those dates keep coming up again and again from different regions, and from comparisons across many regions -- including estimates that are not calibrated by other fossil divergences. This is not an easy "the molecular clock must be wrong" kind of problem.

Nor are the fossils an easy problem. There is pretty good evidence for vertical posture or hindlimb-dominant movement in all of these "hominids." Up to now, we've accepted these kinds of features as de facto evidence of bipedality, and assumed that bipedality is such a unique character of hominids that it is unlikely to be any older. Yet few of these fossils provide really good evidence for obligate bipedality, and some of them provide none at all.

Is it possible that bipedal apes long preceded the divergence of humans and chimpanzees? Was the common ancestor of the two lineages a biped? Or was significant vertical posture a common feature of many Miocene apes -- making Sahelanthropus a possible homologue of Oreopithecus?

Which feature is the important one? The long nuchal plane of Sahelanthropus? The femur neck cortical bone distribution of Orrorin? The toe bone of Ar. kadabba? Heck, I can hardly convince my undergraduates about that toe bone!

I've talked to people about this. Some think that all the molecular stuff is just jibberjabbing, and any day now we will find out that the date estimates were wrong all along.

I think it may be time to start doubting our confidence again.

UPDATE (6/28/2007): I've gotten into rather an interesting e-mail discussion about whether I should have included Homo georgicus on the list of new species. Frankly it didn't occur to me: Wilford didn't mention it.

Actually if you start to think about all the new names that have been proposed in the last 15 years, it is a quite bushy list. It will be no surprise that I think this bushiness has more to do with the listers than the listees.

Anyway, there is something interesting about early Homo right now that goes beyond the simple splitter/lumper questions. I'll have more to say about it in a few days.

References:

Hobolth A, Christensen OF, Mailund T, Schierup MH. 2007. Genomic relationships and speciation times of human, chimpanzee, and gorilla inferred from a coalescent hidden Markov model. PLoS Genet 3:e7. doi:10.1371/journal.pgen.0030007

Patterson N, Richter DJ, Gnerre S, Lander ES, Reich D. 2006. Genetic evidence for complex speciation of humans and chimpanzees. Nature 441:1103-1108doi:10.1038/nature04789

Well, I guess they've got a plot for the pilot of that caveman show:

Humans caught pubic lice, aka "the crabs," from gorillas roughly three million years ago, scientists now report.

Rather than close encounters of the intimate kind, researchers explained humans most likely got the lice, which most commonly live in pubic hair, from sleeping in gorilla nests or eating the apes.

"Sleeping in gorilla nests." Yep, that's the ticket.

The quote is from a LiveScience article by Charles Q. Choi. The article talks a lot about "monkey business" but really spends more time on the hominid-eating-gorilla scenario:

"Unfortunately, even today among modern humans there's a bush meat trade where gorillas are killed for their meat," he said. "If archaic humans were butchering or scavenging those animals 3.3 million years ago, it would be a simple thing to transfer those lice from prey to predator."

UPDATE (3/7/2006): Carl Zimmer's post is great (he's all about the parasites) and mirrors some of what I wrote below. He also includes probably the best snarky quote: "Is this evidence of a Pliocene love that dare not speak its name?"

To telegraph my conclusion a bit, I still think the flawed assumption is that the hominid-gorilla interaction occurred when the hominid and gorilla Pthirus diverged. The interaction works a lot better later, assuming within-gorilla parasite variation. Since there is a lot of within-human variation in the other louse genus, Pediculus, the idea of a couple million years of delay between louse genetic divergence and lateral transfer is not at all unlikely, even without invoking ancient gorilla speciations.

Thoughts

I downloaded the research paper in BMC Biology by Reed and colleagues. Here's the 'Conclusions' section of the abstract:

Reconciliation analysis determines that there are two alternative explanations that account for the current distribution of anthropoid primate lice. The more parsimonious of the two solutions suggests that a Pthirus species switched from gorillas to humans. This analysis assumes that the divergence between Pediculus and Pthirus was contemporaneous with the split (i.e., a node of cospeciation) between gorillas and the lineage leading to chimpanzees and humans. Divergence date estimates, however, show that the nodes in the host and parasite trees are not contemporaneous. Rather, the shared coevolutionary history of the anthropoid primates and their lice contains a mixture of evolutionary events including cospeciation, parasite duplication, parasite extinction, and host switching. Based on these data, the coevolutionary history of primates and their lice has been anything but parsimonious.

There is actually a much more interesting story here than is indicated in either press account or abstract. The genera Pediculus and Pthirus were thought to have diverged at the time that gorillas diverged from the chimpanzee-human clade. This would explain why gorillas have Pthirus and chimpanzees Pediculus. The fact that humans have both ... well, that remained unexplained. The purpose of the study was to test whether humans retained the two genera ancestrally, or if instead they picked one up later.

What they found is that the two genera didn't diverge at the gorilla-chuman split, but instead way earlier. Their estimate for the Pediculus-Pthirus divergence is 13 million years. Thirteen million is as much as twice the age of the human-gorilla common ancestor. This estimate is probably biased toward the recent side, since it is calibrated against a divergence between hominoid and baboon lice assumed at 22.5 million years ago -- probably more recent than the true hominoid-baboon divergence.

The paper considers it likely that the human-gorilla-chimpanzee common ancestor lineage maintained this pair of lice species for the intervening time period, with one genus being lost in each of the two (gorilla and chuman) descendant clades. This ancestral lineage would be similar to humans in that respect -- host to two distinct parasite lineages, both of which stemmed from a single ancestor species.

But much later than the chimpanzee-human divergence, humans apparently picked up the gorilla lice somehow. The paper doesn't belabor this point or attempt to explain it, beyond this:

Evidence suggests that Pthirus pubis has been associated with humans for several million years, and likely arrived on humans via a host switch from gorillas. Despite the fact that human pubic lice are primarily transmitted via sexual contact, such contact is not required to explain the host switch. Parasites often switch from a given species to a predator of that species [17], and are sometimes found to switch to unrelated hosts in communally used areas, such as roosting or nesting sites [18]. The host switch in question could have resulted from any form of contact between archaic humans and gorillas including, but not limited to, feeding on or living among gorillas. Regardless of how the transfer occurred, suitable habitat had to be available on the new human host for the host switch to be successful. For example, it is possible that the switch of Pthirus from gorillas to humans coincides with a change in available niche space in humans, such as the loss of body hair. Further study, however, is required to test such a hypothesis (Reed et al. 2007:7).

Hominids were certainly not hunting gorillas 3.3 million years ago. At least, not the hominids we know about. That date is a bit older than Lucy; it's 700,000 years older than the earliest evidence of flaked stone and 800,000 earlier than the earliest evidence of antelope butchery. Hominids weren't hunting gorillas because they weren't hunting any large mammal species then.

What's worse, gorillas and hominids weren't sympatric 3.3 million years ago. At least, not the gorillas and hominids we know about. Unless gorillas ranged into open woodland, and in particular the East African coastal forest, or hominids ranged into the central or west African rain forest, they never came into contact with each other at all.

If anything, we might expect that gorillas and chimpanzees would have been likely to come into contact and exchange parasites. They are currently sympatric, they eat the same foods, and they even build similar sorts of nests. It's like they share the same locker room. But they didn't have this parasite exchange.

It's all very strange. First we have this long period of divergence of the two great ape louse genera (orangutans don't have their own louse species). Then we have a divergence of the human and chimpanzee Pediculus species just exactly when it should have happened. And then there is this lateral transfer of lice from gorillas to humans 3 million years ago - when hominids and gorillas weren't apparently sympatric and had no credible mechanism for lice exchange.

Here's my hypothesis: cryptic African hominoids. The apparent craziness all comes from the assumption that the only species that existed are the ones we know about. For Africa 3 million years ago, that means two or three hominid species, one gorilla lineage and one chimpanzee lineage. We don't have any fossils that old for the apes; we can only infer their existence from the fact that they exist now.

Let's consider what we know. We know that 3 million years ago there weren't any chimpanzee or gorilla relatives in the Rift Valley, and plausibly (but not definitely) not in South Africa or the Sahel.

We don't know how extensively hominids ranged into the west African or central African forests, particularly from the north and southeast. We don't know how extensively gorillas and/or chimpanzees may have ranged outside the core forested areas where they have historically existed. In the absence of Homo, the competition between these apes and hominids at the forest boundaries may have been a close game.

We don't know how many species of ancient chimpanzees and gorillas there may have been. The present subspecific variation of chimpanzees seems to reflect recent colonization of the eastern range from central Africa, and some substantial population interchange between central and western ranges. Gorilla subspecies now seem to have emerged within the same time frame, with a possible colonization from their western range into their eastern range within the past million years.

Bonobos are only ca. 850,000 years old (Won and Hey 2005). To summarize, the current eastern chimpanzees weren't in East Africa half a million years ago, and the bonobos weren't south of the Congo a million years ago, and eastern gorillas weren't there a million years ago either.

Who was? It seems to me that the best candidates would be ancient species of gorillas and chimpanzees that no longer exist. A second-best (and maybe more interesting) candidate is some variety of hominid. A third-best (and even more interesting) candidate is an ancient ape lineage dating from before the G-C-H divergence.

Three million years ago, any one of those possibilities is credible. Here's my favorite: two gorilla species (or subspecies) became isolated enough for louse divergence 3.3 million years ago, and continued to coexist. Sometime after 2 million years ago, Homo encountered one of these species and picked up its lice. That gorilla lineage later became extinct, perhaps by range expansion from Homo.

Oh, and the long divergence time between the two lice genera? I like a long divergence and later lateral transfer from some pre-H-C-G Miocene ape lineage. There were likely several in Africa to choose from. Maybe it was Sahelanthropus...

References:

Reed DL, Light JE, Allen JM, Kirchman JJ. 2007. Pair of lice lost or parasites regained: the evolutionary history of anthropoid primate lice. BMC Biol 5:7. doi:10.1186/1741-7007-5-7

Won Y-J, Hey J. 2005. Divergence population genetics of chimpanzees. Mol Biol Evol 22:297-307.

One of the most important mechanisms of genetic evolution is gene duplication. There are a few well-known gene families, such as the globin gene family, whose several members have diverged over hundreds of millions of years from a single ancestral gene. Each globin gene is the product of one or more duplications.

Googling through some papers, this line got my attention:

The divergence of gene expression between human duplicate genes is rapid, probably faster than that between yeast duplicates in terms of generations.

That's from Makova and Li (2003). You have to admit, it's attention-getting. Human gene expression differentiating faster than yeast?

It's about genes that have duplicated during recent evolution. When one gene becomes two, the tendency is to think the newly arrived copy will be neutral. But things are not simple -- two copies of a gene complete with associated regulatory sequences may end up making twice as much of the gene product. Occasionally that may be a good thing, but often it will be bad. So selection affects gene duplicates the same way it affects anything else.

But duplicate copies of genes present an interesting possibility: they may come to be regulated differently. This can happen if both copies retain their regulatory machinery, but some part of the regulatory chain of one copy is changed by mutation. Or it can happen if the gene duplication does not duplicate all the regulatory sequence -- for example, if it is located some considerable distance upstream from the original copy.

Makova and Li (2003) examined one kind of change in gene expression -- when different copies start to be expressed in different tissues. This kind of change is fairly easy to understand in terms of regulatory sensitivity. Different tissues express different regulatory proteins and RNAs, and regulatory sequences of genes are more or less sensitive to these different parts of the regulatory machinery. Sequence rearrangements may displace the coding sequence farther from inhibitor sites, or may decrease the chance of methylation, or may place the new copy next to a highly transcribed region. Sequence changes can remove an enhancer site, or make a transcript more susceptible to RNA interference, or any number of other changes. There are many, many possibilities for regulatory divergence.

The timescale of expression divergence studied by Makova and Li (2003) is fairly long:

We found that a large proportion of human duplicate genes have diverged rapidly in their spatial expression. Assuming that the average synonymous rate in higher primates is 1.5 x 10^-9 nucleotide substitutions per site per year (Yi et al. 2002), 75.5% of human paralogs diverge in their expression in at least one tissue after only 25 Myr (K_S = 0.068).

Clearly, "rapid" is a relative term. Here, we are looking at functional divergence of duplicate genes over the time occupied by the divergence of the hominoids from early Miocene apes to the present. Some proportion of these changes have occurred during the past few million years of human evolution, and may be among the genetic changes that led to the evolution of human-specific characters.

However, the broadest functional category represented by genes that differentiated functions after duplication was immune response:

It is interesting to look into the functions of duplicate genes that show rapid divergence in expression. Thus, we investigated the functions of the duplicate gene pairs with KS < 0.3 and with diverged expression (as presence or absence of expression in a tissue) in at least 50% of the tissues studied (we considered only the tissues in which at least one gene of a pair is expressed). There were 38 such gene pairs (Table 1). Also, we examined duplicate gene pairs with KS < 0.3 and a correlation coefficient of gene expression (R) < 0.5. There were 18 gene pairs in this group (Table 1). Interestingly, most of the gene pairs in these two groups overlapped. Thus, the results from the two measures concur. The functions of these genes were retrieved from LocusLink (http://www.ncbi.nlm.nih.gov/LocusLink/) manually. The gene pairs in these two groups encode enzymes (oxidoreductases, hydrolases, transferases, and an isomerase), proteins of the immune system (e.g., lymphocyte antigen, cytokine gro-beta, MHC proteins, and immunoglobulins), transcription factors, structural proteins (e.g., amelogenin, keratin, and skeletal muscle protein), and receptors (Table 1). To determine whether any of the functions were overrepresented among genes with rapid divergence in expression, we compared their functions with the functions of the other duplicate genes using the Gene Ontology database (Camon et al. 2003). There was indeed a significantly higher proportion of immune response genes among gene pairs with rapid divergence in expression compared with other gene pairs in our study (P < 0.009 for gene pairs with KS < 0.5 and diverged expression in at least 50% of studied tissues; P < 0.001 for gene pairs with KS < 0.5 and R < 0.5).

They also found that two-thirds of the duplicate genes that didn't diverge in expression were genes that are normally expressed in nearly all tissues -- in other words "ubiquitously expressed" genes. This finding has been confirmed by later work (for example, Yang, Su and Li 2005; Liao and Zhang 2006). Liao and Zhang (2006) showed that the degree of evolution in gene expression profile is negatively associated with gene expression level -- that is, more highly expressed genes evolve more slowly. This is paralleled by the observation that sequence evolution is slower for more highly expressed genes. Yang et al. (2005) showed that narrowly expressed genes (those expressed in few tissues) evolve faster than those expressed more broadly.

All these observations tend to support the idea that pleiotropic constraints are important limits to adaptive evolution. Gene duplication followed by functional divergence is one of the main ways that genetic correlations among different phenotypic characters can be decoupled. If a gene duplication can allow a single gene with two phenotypic effects to become two genes each with one phenotypic effect, then it can erase pleiotropic constraints on evolutionary change.

It's a way of opening new pathways to the evolution of complex phenotypes.

About the yeast thing: Naturally, the possibilities for regulatory divergence are higher in vertebrates than in yeast. Vertebrates have substantial differentiation of tissue types, complex developmental programs, and differential gene expression. So it's no real surprise that vertebrates should have seen more rapid regulatory evolution than yeast in this respect. But it does show that this kind of duplication and subsequent functional differentiation is a potentially rapid pattern of evolutionary change compared to other patterns of change.

References:

Liao B-Y, Zhang J. 2006. Low rates of expression profile divergence in highly expressed genes and tissue-specific genes during mammalian evolution. Mol Biol Evol 23:1119-1128. doi:10.1093/molbev/msj119

Makova KD, Li W-H. 2003. Divergence in the spatial pattern of gene expression between human duplicate genes. Genome Res 13:1638-1645. doi:10.1101/gr.1133803

Yang J, Su AI, Li W-H. 2005. Gene expression evolves faster in narrowly than in broadly expressed mammalian genes. Mol Biol Evol 22:2113-2118. doi:10.1093/molbev/msi206

I happened into a post on Uncertain Principles soliciting candidates for "Most annoying misconception about your field". The choice there was the nature of the Heisenberg Uncertainty Principle.

RPM at Evolgen posted an annoying genetics misconception, namely:

the idea that by sequencing a genome, we are "decoding" it

Personally, I think this would be a great topic for a meetings panel. I can think of about fifty really annoying misconceptions. The nature of these two seems especially science-fiction-y -- the sort of thing that people generally knowledgeable about science sort of understand to be true or meaningful.

On that level, I would nominate the one-gene, one-trait fallacy -- the idea that every trait is encoded by one gene. From this we have the popular idea that you can discover a gene "for" something. Of course, the usual case is that you discover a gene with a particularly bad allele in some people with a genetic disorder. But that generally gives little clue about what the gene does, or what its evolutionary history might be.

But that isn't actually the one that annoys the most.

Instead, I am most annoyed by the idea that genetic divergence and species divergence are the same. That fallacy underlies the long literature on the 5-million-year divergence date for chimpanzees and humans.

Set aside for a moment the fact that the species divergence must be at least old enough to encompass the earliest fossil hominids (now, around 6 million years old or so). The real problem is that two newly-isolated populations are not genetically uniform -- each of them has variation and the two overlap to some extent. The date of genetic divergence between alleles taken from each of the populations at the time of their isolation is a function of the demographic and selection histories in their common ancestor population.

So genetic divergence must always precede species divergence. That period of time probably ranges from a few hundred thousand to several million years before the time of species divergence.

It's an important problem in the human-chimpanzee case, since the 5-million-year genetic divergence would correspond to a younger species divergence. Genetics are even more out of tune with the fossils than most people usually assume. (The problem is likely in accurately estimating the rate of genetic changes.)

And it's always annoying to see that 5-million-year figure repeated endlessly when, not only does it have to be wrong, it shouldn't have even been applicable in the first place.